Widely prescribed pharmaceuticals for health disorders such as insomnia and erectile dysfunction target only the biochemical physiology of the affliction, ignoring the psychological component. This is a wasted opportunity, since as a byproduct of successful physiological outcomes, drugs for disorders such as insomnia and erectile dysfunction can provide afflicted individuals with temporary relief of anxiety associated with the condition. However, this psychological “fix” is only temporary, and existing pharmaceutical therapies neglect the opportunity to capture or consolidate the favorable psychological response. Instead, an afflicted individual's anxiety regarding the disorder can return, often provoking or exacerbating a relapse of the disorder.
Classical fear conditioning occurs when an affectively neutral stimulus is paired with a noxious aversive stimulus (unconditioned stimulus [US]) such as footshock. Afterward, the previously neutral stimulus (i.e., now the conditioned stimulus [CS]) is able to elicit a variety of autonomic, hormonal, and skeletal responses that accompany the conscious experience of fear in humans and which are used to operationally define fear in laboratory animals. The fear-eliciting properties of the CS can be extinguished by repeatedly presenting the CS in the absence of the US. It is generally believed that extinction does not reflect unlearning of the original association but involves instead the formation of new associations that compete with the previously conditioned response.
Recent results in the field of cognitive neuroscience have demonstrated that a drug that enhances learning can consolidate a favorable psychological response to a stimulus (WO 02/078629, incorporated herein by reference in its entirety). This result has been very important in the treatment of phobic disorders, as a recent clinical study has shown that subjects undergoing cognitive behavioral therapy require substantially fewer sessions to reach clinical cure (e.g., 75% fewer) if they are administered a drug that enhances learning in conjunction with their therapy sessions (Davis, Arch Gen Psychiatry. 2004; 61:1136-1144). A suitable drug for enhancing learning is D-cycloserine (“DCS”). DCS is an FDA-approved, off-patent, second-line treatment for tuberculosis (trade name Seromycin®, hereafter “DCS”, sold by Eli Lilly), with a side effect of enhanced learning, although chronic administration tends to limit or even reverse this effect. Other cognitive enhancers, in particular other glycine partial NMDA receptor agonists, are also believed to be effective.
Accordingly, the prior art describes treatments for phobic disorders comprising behavioral cognitive therapy in conjunction with acute administration of pharmaceuticals that enhance learning.
The prior art also describes chronic administration of NMDA agonists to treat Alzheimer's Disease and neuropsychiatric disorders. U.S. Pat. No. 6,228,875 describes administering 105-500 mg doses of DCS (or other NMDA receptor agonists) on a chronic basis to treat schizophrenia, attention deficit disorder, and other neuropsychiatric disorders. It does not teach the advantages of administering acute doses of DCS in conjunction with other drugs.
The prior art does not describe treatments of other disorders such as depression, insomnia, erectile dysfunction, and chronic pain by combining pharmaceutical treatments for those conditions with acute administration of pharmaceuticals that enhance learning.
There is a long-felt need in the art for compositions and methods for enhancing the treatment of diseases and disorders which have anxiety components. The present invention satisfies those needs.